Treatment of tumours by hyperthermia (41 degrees minus 44 degrees) causes a marked regression and the investigation is designed to study the role of lysosomal enzyme activation and damage to the lysosomal membranes in the regression. Effects of hyperthermia will be compared with those of irradiation and the responses of lysosomes of normal tissues will be compared with those of tumours. Studies will be made of the lysosomes of Hela cells after treating the cells for various times at temperatures within the range 40 degrees minus 45 degrees. Cells will also be irradiated with gamma-rays and the effect of combined irradiation and hyperthermia studied. The response of lysosomal enzymes of spontaneous mouse mammary tumours and transplanted tumours to hyperthermia will be studied. Special attention will be devoted to lysosomal enzyme activation and to changes in the permeability of the lysosomal membrane both of which will be studied using a quantitative histochemical technique. Effects of labilisers of lysosomal membranes will be studied in conjunction with hyperthermia and irradiation. The objective of the research is, by gaining a better understanding of lysosomal enzyme activation, to improve the therapy of tumours in man.